The hydroamination of internal alkynes via tandem rhodium-catalysis gives branched N-allylic indolines with high regio- and enantioselectivity. An acid-switch provides access to the linear isomer in preference to the branched isomer by an isomerization mechanism. Mechanistic studies suggest formation of an allene intermediate, which undergoes hydroamination to generate allylic amines instead of the enamine or imine products typically observed in alkyne hydroaminations.
Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons' survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials.
Purpose This study was undertaken to elucidate the clinical significance of widening of the popliteal hiatus on magnetic resonance imaging (MRI), and to document the clinical results and technical aspects of arthroscopic repair of this finding. Methods Included are 82 knees after arthroscopic surgery, divided according to arthroscopic diagnosis into group A, hypermobility of lateral meniscus, 8 knees; group B, tear of the anterior horn of the lateral meniscus, 32 knees; and group C, no abnormality of the lateral meniscus, 36 knees with medial meniscal tears and 6 with other conditions. Popliteal hiatus diameter was measured and the popliteal hiatus/lateral tibial plateau (LTP) ratio was calculated on preoperative sagittal and coronal MRI. At arthroscopy, the widened popliteal hiatus in group A was tightened anteriorly by outside-in or all-inside suture and posteriorly with all-inside suture. Outcomes were evaluated with MRI, Lysholm, Tegner and VAS scores.
ResultsThe preoperative diameter of the popliteal hiatus and the popliteal hiatus/LTP ratio were significantly larger in group A than in groups B and C (p < 0.05) on both views. Threshold popliteal hiatus/LTP values of 0.16 and 0.18 on the sagittal and coronal views demonstrated diagnostic discrimination, and these values were significantly reduced after arthroscopy in Group A. Lysholm and Tegner scores were improved after tightening of the popliteal hiatus, while VAS scores reduced (all p < 0.05). Conclusion Widening of the popliteal hiatus on MRI may lead to recurrent subluxation of the lateral meniscus. Arthroscopic anterior and posterior tightening of the popliteal hiatus was a safe and effective treatment. Level of evidence II.
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